HPE Chronic pain – part two | Page 9

SCIENCE PHOTO LIBRARY (such as post-operative pain). 44 When compared with typical opioids such as oxycodone, tapentadol improves the health-related quality of life and functional outcomes of patients with chronic pain due to osteoarthritis and low back pain significantly. 42 In the 36-item Short Form Health Survey, tapentadol showed significantly greater improvements from baseline than oxycodone in physical and mental component summary scores and all subscale scores except general health. 45 In an exploratory study, both tapentadol and oxycodone produced respiratory depression. Tapentadol 100mg (but not 150mg) had a modest respiratory advantage over oxycodone 20mg. 46 With regard to other adverse effects, again the lower mu-opioid effect results in significantly fewer gastrointestinal adverse events (nausea, vomiting and constipation) compared with typical opioids such as oxycodone 41 (for constipation even when compared with the slow-release combination of oxycodone/naloxone). 47 A network meta-analysis of opioid analgesics for chronic pain identified tapentadol as the opioid with the lowest incidence of overall adverse events, including constipation, and the lowest trial withdrawal rate. 48 Similarly, after three months administration, testosterone depression was less with tapentadol than with oxycodone. 47 Data on the effect of tapentadol on immune function are limited, but experimental data show maintenance of splenic cytokines with acute and chronic use. 49 Buprenorphine Buprenorphine has a complex pharmacology. It is a potent but partial agonist of the mu-opioid receptor, showing a high affinity but low intrinsic activity and slow dissociation (half-life 2–5 hours). 50–52 It also displays kappa-receptor antagonism, 51 agonism at the nociceptin or opioid-receptor-like 1 receptor 53 and antagonism at delta-opioid receptors. Buprenorphine is widely used in a sublingual preparation for treatment of pain, 54 but, in particular, for opioid substitution in opioid addiction. 55 Sublingual buprenorphine provides similar analgesic efficacy to intramuscular or intravenous morphine. 56 Due to its high potency and lipophilicity, buprenorphine can be used through transdermal delivery systems. 57 These have provided equivalent analgesia to morphine, hydromorphone, oxycodone, fentanyl and methadone. 53 In experimental settings, buprenorphine has a ceiling effect for respiratory depression; 58,59 however, fatalities due to respiratory depression have occurred 60 but none are reported with transdermal buprenorphine in a data analysis from US poison centres. 61 Buprenorphine seems to cause less tolerance than typical opioids such as fentanyl, 62 has anti-hyperalgesic effects 63 and may attenuate OIH 64 with less glia cell activation via toll-like receptor 4. 65 In animal experiments, buprenorphine seems to be less immunosuppressive. 66,67 Buprenorphine also causes less OPIAD than typical opioids. 68 It is also less constipating as a transdermal preparation than even transdermal fentanyl 52 and causes less cognitive dysfunction than typical opioids, 53 a possible explanation for its lower fracture risk due to falls. 69 Buprenorphine, like all other opioids, is associated with misuse and diversion, in particular in its sublingual preparation, where it is used as substitution therapy in an at-risk population. 70 Poison Control Centre data showed that the 7-day transdermal patch had lower prescription-adjusted rates of intentional abuse and suspected suicidal intent than all typical opioids (morphine, oxycodone, oxymorphone, methadone and transdermal fentanyl) in the US. 61 Conclusions Over the last 30 years, a number of analgesics have been identified that have similar analgesic efficacy to typical strong opioids such as morphine, oxycodone and fentanyl but whose activity is not mediated exclusively by the mu receptor. This has resulted in the suggestion to refer to the newer medications as ‘atypical opioids’. This term currently describes buprenorphine, tramadol and tapentadol and this separation is not only pharmacologically important but also clinically useful because these medications differ from the typical opioids with regards to safety and tolerability. A recent attempt to characterise atypical opioids introduces the term mu-load as the percent contribution of the mu-opioid component to the adverse effect magnitude relative to a pure/classical mu-opioid at equianalgesic doses. 71 While typical opioids have by definition a mu-load of 100%, atypical opioids would have a mu-load <100%. As an example, tapentadol, using respiratory depression and constipation, has a mu-load ≤40%. 71 This concept enables the objective quantification of atypical opioids and thereby supports this new terminology. hospitalpharmacyeurope.com | 2020 | 9